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Stanol esters decrease plasma cholesterol independently of intestinal ABC sterol transporters and Niemann-Pick
F Jeffrey Field1, Ella Born, Satya N Mathur
1Department of Veterans Affairs, University of Iowa, Iowa City, IA 52242, USA. f-jeffrey-field@uiowa.edu
Journal of Lipid Research
|September 3, 2004
Summary
Plant stanol esters effectively lower cholesterol by mechanisms independent of intestinal sterol transporter gene expression. Cholesterol flux impacts ABC transporter expression, but not NPC1L1, suggesting distinct roles for these proteins.
Area of Science:
- Biochemistry
- Molecular Biology
- Nutritional Science
Background:
- Plant stanol esters are known for their cholesterol-lowering properties.
- The precise molecular mechanisms underlying their efficacy, particularly involving intestinal sterol transporters, require further elucidation.
Purpose of the Study:
- To investigate the impact of plant stanol esters on cholesterol metabolism in hamsters.
- To examine the relationship between stanol ester consumption and the mRNA expression of key intestinal sterol transporters, including ABCA1, ABCG1, ABCG5, ABCG8, and NPC1L1.
Main Methods:
- Hamsters were fed diets containing plant stanol esters, cholesterol, or a combination of cholestyramine/lovastatin.
- mRNA levels of specific sterol transporters (ABCA1, ABCG1, ABCG5, ABCG8, NPC1L1) were quantified in the duodenum, jejunum, and ileum.
- Plasma cholesterol and plant sterol levels were measured.
Main Results:
- Plant stanol esters reduced plasma cholesterol by 36%, while cholestyramine/lovastatin reduced it by 94%.
- Cholesterol feeding increased plasma cholesterol, and stanols accumulated in enterocytes.
- Stanol ester and cholestyramine/lovastatin treatments decreased ABCG5 and ABCG8 mRNA levels.
- Cholesterol feeding increased ABCA1 and ABCG1 expression, but NPC1L1 mRNA levels were not significantly altered by any diet.
- Distinct cellular localization patterns were observed for ABCA1 compared to other transporters.
Conclusions:
- The cholesterol-lowering effect of plant stanol esters appears unrelated to alterations in the mRNA levels of intestinal ABC sterol transporters or NPC1L1.
- Intestinal cholesterol flux influences ABC transporter expression, but not NPC1L1.
- The differential localization of ABCA1 suggests a unique functional role compared to ABCG1, ABCG5, ABCG8, and NPC1L1.